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Efficacy Study of Riociguat and Its Effects on Exercise Performance and Pulmonary Artery Pressure at High Altitude

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02024386
First Posted: December 31, 2013
Last Update Posted: April 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Richard Moon, Duke University Medical Center
  Purpose
During ascent to high altitude there is a physiologic response to hypoxia that results in an elevated pulmonary arterial pressure associated with decreased exercise performance, altitude-induced pulmonary hypertension, and high altitude pulmonary edema (HAPE). Riociguat is a novel agent from Bayer Pharmaceuticals that has already demonstrated effectiveness in the treatment of pulmonary hypertension, and it may prove to be beneficial in cases of altitude-induced pulmonary hypertension or HAPE. This research study, composed of 20 healthy volunteers ages 18-40 years, will attempt to mimic the decreased oxygen supply and elevated pulmonary artery pressures found in conditions of high altitude, allowing observation of the effects of riociguat and exercise on pulmonary arterial pressure, arterial oxygenation, and exercise performance. Prior to entering the hypobaric chamber, subjects will have radial arterial lines and pulmonary artery catheters placed to obtain arterial and pulmonary artery pressure measurements. Subjects will then enter the hypobaric chamber and perform exercise tolerance tests at a simulated altitude of 15,000 feet on an electrically braked ergometer (exercise bike) before and after administration of riociguat. If, after administration of riociguat and exposure to a simulated altitude of 15,000 feet, the exercise performance is improved and observed pulmonary artery pressures are lower than those measurements seen prior to administration of riociguat, this could lead to development of a prophylactic and/or treatment strategy for HAPE and high-altitude pulmonary hypertension. Statistical analysis will compare the variables of pulmonary artery pressure, radial arterial pressure, ventilation rate, cardiac output, PaO2, and work rate at exhaustion before and after administration of the drug riociguat. The investigator's hypothesis is that riociguat will decrease pulmonary artery pressure and improve gas exchange and exercise performance at altitude.

Condition Intervention Phase
Hypertension, Pulmonary Altitude Sickness Drug: Riociguat Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The Effect of Riociguat on Gas Exchange, Exercise Performance, and Pulmonary Artery Pressure During Acute Altitude Exposure

Resource links provided by NLM:


Further study details as provided by Richard Moon, Duke University Medical Center:

Primary Outcome Measures:
  • Mean Pulmonary Artery Pressure [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Subject pulmonary artery pressures will be continuously monitored during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).


Secondary Outcome Measures:
  • Mean Radial Arterial Pressure [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Subject systemic arterial pressures will be continuously monitored via radial artery catheterization during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).

  • Mean Arterial Oxygen Saturation (SaO2) [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Subject arterial oxygen saturation (SaO2) will be periodically monitored at fixed intervals via arterial blood gas measurements during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).

  • Mean Ventilation Rate [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Subject ventilation rates will be monitored continuously using a multi-channel A/D converter (PowerLab™) connected to a personal computer, using Chart™ software (ADInstruments, Colorado Springs, CO) during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).

  • Mean Work Rate at Exhaustion [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Subject work rates at exhaustion (in watts) will be continuously monitored using an ergometer (exercise bicycle) during the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Measurements will be obtained at rest, every 3 minutes during the exercise test (referred to as a stage below) and at 5 minutes post exercise. Results will be reported as a 30 second average. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).

  • Cardiac Output [ Time Frame: At rest, every 3 minutes during the exercise test and 5 minutes after each exercise test ]
    Arterial blood samples will be obtained before, during, and after the VO2max exercise test in the hypobaric chamber at a simulated altitude of 15,000 feet. Exercise level will be increased every 3 minutes until test termination criteria are achieved. Samples will be obtained during the fifth minute of rest prior to exercise, during the third minute of each exercise level (referred to as stage below) and during the fifth minute post exercise. Cardiac output (CO) will be calculated using the Fick Principle: CO = V̇O2/(CaO2 - Cv̄O2) where CaO2 and Cv̄O2 represent the arterial and mixed venous oxygen content, respectively. CaO2 and CvO2 will be determined from analysis of the arterial blood samples using an IL GEM 4000 analyzer. VO2 will be reported as the final 30 secon average value of each stage. Subjects in the Riociguat cohorts will be tested prior to receiving drug and 90 minutes after receiving drug (midway through a three hour rest period between altitude exposures).


Enrollment: 28
Study Start Date: January 2014
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riociguat 0.5 mg
Riociguat 0.5 mg tablets, one-time oral dose of 0.5 mg
Drug: Riociguat
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. Riociguat will be administered at the 90-minute mark of this rest period.
Other Names:
  • Adempas
  • NDA 204819
Experimental: Riociguat 1.0 mg
Riociguat 0.5 mg tablets, one-time oral dose of 1.0 mg
Drug: Riociguat
After completion of first V02 max test at altitude, subjects will have a 3-hour rest period. Riociguat will be administered at the 90-minute mark of this rest period.
Other Names:
  • Adempas
  • NDA 204819
No Intervention: Control arm
No drug

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males and females
  • Non-smoking
  • Non-pregnant females
  • Ages 18 - 40 years old

Exclusion Criteria:

  • Serious pulmonary or cardiovascular comorbidities
  • Pregnant women
  • VO2max < 35 mL/kg per minute
  • Sickle cell trait or disease
  • Smokers
  • Lung disease
  • Hypertension
  • Cardiac disease and left bundle branch block
  • Taking nitrates, nitric oxide donors (such as amyl nitrite), and phosphodiesterase (PDE) inhibitors (including specific PDE-5 inhibitors, such as sildenafil, tadalafil, or vardenafil, or non-specific PDE inhibitors, such as dipyridamole or theophylline).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02024386


Locations
United States, North Carolina
Duke Center for Hyperbaric Medicine and Environmental Physiology, Trent Drive, Building CR2, Room 0584, Box 3823,
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Richard Moon
Investigators
Principal Investigator: Richard E Moon, MD Duke University
  More Information

Publications:

Responsible Party: Richard Moon, Medical Director, Duke Center for Hyperbaric Medicine and Environmental Physiology, Professor of Anesthesiology, Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02024386     History of Changes
Other Study ID Numbers: Pro00049150
First Submitted: December 18, 2013
First Posted: December 31, 2013
Results First Submitted: December 19, 2016
Results First Posted: April 12, 2017
Last Update Posted: April 12, 2017
Last Verified: March 2017

Keywords provided by Richard Moon, Duke University Medical Center:
Guanylate Cyclase
Pulmonary Edema of Mountaineers
Mountaineering
Performance-Enhancing Substances
Athletic Performance

Additional relevant MeSH terms:
Hypertension, Pulmonary
Altitude Sickness
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders